The objective of this program is to expand and strengthen the capabilities of Florida A&M University (FAMU) investigators in biomedical research, to provide undergraduate students with "hands-on" experience in the fundamentals of scientific research and to motivate them to pursue biomedical research careers as well as to train graduate students in state of the art research in the biomedical sciences with concentration in pharmacology, medicinal chemistry, biochemistry, molecular biology and toxicology. The proposed research program will involve studies using laboratory animals. The subprojects have the following topics: (1) An Electrochemical Study of Environmental and Metabolic Xenobiotic Oxidation; (2) Sequence Analysis of -Actinin Gene and Its Regulation by Thyroid Hormones; (3) Selenium Compounds and Cadmium Toxicity on Lungs; (4) Colchicine and Taxol Analogs as Probes of Tubulin; (5) Biologically Active Substances Produced by Antarctic Cryptoendolithic Fungi; (6) Connective Tissue changes in Overused Skeletal Muscles; (7) Nonimmunologic Activation-Secretion Coupling in Mast Cells; (8) disorder of Metenkephalin Levels in Diabetes; (9) Molecular Mechanisms of Chromate and Cadmium Toxicity in Mammalian Systems; (10) Derivatives of Corticosteroid Metabolites; (11) The Role of Calcium in the Cytotoxicity of Chlorophenols; (12) Use of Differential Scanning Calorimetry to Study Apolipoprotein and Pancreatic Lipase; (13) Synthesis and Biological Activity Determinations of Some N-Aminotetrahydropyridines; (14) Comparison of Three Insulin-Resistant Models on Drug Metabolism in Rats; (15) Developing an Animal Model for Response to Pentobarbital; (16) Zinc Dietary Alterations of Cadmium-Induced Hepatic Toxicity in Rats; (17) Neonatal Lead Exposure Effects on the Adrenal Cortex Function; (18) Neurochemical Basis of the Beneficial Effects of Chronobiotic Drugs. Analytical procedures including spectral determinations (e.g., ultraviolet, infrared, proton NMR, 31-P NMR atomic absorption), chromatographic work (e.g., TLC, GC, HPLC) and many pharmacological assays using scintillation counters will be routinely conducted in these investigations. Both the graduate and undergraduate students will be involved in the planning and execution of the experiments.